title: No evidence for association between bipolar disorder risk gene variants and brain structural phenotypes.
abstract: BACKGROUND
  While recent genome-wide association studies have identified several new bipolar disorder (BD) risk variants, structural imaging studies have reported enlarged ventricles and volumetric reductions among the most consistent findings. We investigated whether these genetic risk variants could explain some of the structural brain abnormalities in BD.
  
  
  METHODS
  In a sample of 517 individuals (N=121 BD cases, 116 SZ cases, 61 other psychosis cases and 219 healthy controls), we tested the potential association between nine SNPs in the genes CACNA1C, ANK3, ODZ4 and SYNE1 and eight brain structural measures found to be altered in BD, and if these were specifically affecting the BD sample. We also assessed the polygenic effect of all these 9 SNPs on the brain phenotypes.
  
  
  RESULTS
  Our most significant result was an association between the risk allele A in CACNA1C SNP rs4775913 and decreased cerebellar volume (pnom.=0.0075) in the total sample, which did not remain significant after multiple testing correction (pthreshold<0.0064). There was no evidence for diagnostic specificity for this association in the BD group. Further, no polygenic effect of these 9 SNPs was observed.
  
  
  CONCLUSIONS
  Low statistical power might increase our type II error rate.
  
  
  CONCLUSIONS
  The present findings indicate that these risk SNPs do not explain a large proportion of the structural brain alterations in BD. Thus, these genes which are all related to neuronal functions must be involved in other pathophysiological aspects of BD development.
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Oslo, Norway. m.s.tesli@medisin.uio.no
authors.forename: Martin
authors.initials: M
authors.lastname: Tesli
authors.forename: Randi
authors.initials: R
authors.lastname: Egeland
authors.forename: Ida E
authors.initials: IE
authors.lastname: Sønderby
authors.forename: Unn K
authors.initials: UK
authors.lastname: Haukvik
authors.forename: Francesco
authors.initials: F
authors.lastname: Bettella
authors.forename: Derrek P
authors.initials: DP
authors.lastname: Hibar
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
authors.forename: Lars Morten
authors.initials: LM
authors.lastname: Rimol
authors.forename: Ingrid
authors.initials: I
authors.lastname: Melle
authors.forename: Ingrid
authors.initials: I
authors.lastname: Agartz
authors.forename: Srdjan
authors.initials: S
authors.lastname: Djurovic
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
mesh_terms: D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000033:anatomy & histology / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable
keywords: ANK3; Bipolar disorder; CACNA1C; Genetics; MRI; Schizophrenia